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- Title
Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response.
- Authors
Lewis, J P; Fisch, A S; Ryan, K; O'Connell, J R; Gibson, Q; Mitchell, B D; Shen, H; Tanner, K; Horenstein, R B; Pakzy, R; Tantry, U S; Bliden, K P; Gurbel, P A; Shuldiner, A R
- Abstract
A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported to be a major determinant of clopidogrel response. This variant was genotyped in 566 participants of the Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R was not associated with pre- or post-clopidogrel platelet aggregation in the PAPI study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P = 0.91, respectively). The Q192 allele was not associated with cardiovascular events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20-1.06; P = 0.07). No correlation was observed between paraoxonase activity and post-clopidogrel platelet aggregation (r(2) < 0.01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post-clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response.
- Publication
Clinical pharmacology and therapeutics, 2011, Vol 90, Issue 4, p568
- ISSN
1532-6535
- Publication type
Journal Article
- DOI
10.1038/clpt.2011.194